Propranolol for Vascular Responses in Menopause

(2100208 Trial)

Overseen By Jacqueline Limberg

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Missouri-Columbia

Must not be taking: Prescription medications

Disqualifiers: Pregnancy, Smoking, Diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 1-2 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study how blood vessels respond to changes in oxygen and carbon dioxide levels in women at different stages of menopause. It will test the effects of three treatments: Gemtesa, Propranolol (a beta-blocker that affects heart rate and blood flow), and a placebo. Participants will undergo a series of tests, including breathing low-oxygen or high-carbon dioxide air and a cold water test on their foot. Women who are pre-, peri-, or post-menopausal, assigned female at birth, and have a healthy weight might be a good fit for this study. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants a chance to contribute to groundbreaking medical knowledge.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current prescription medications to participate in this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that propranolol is usually well-tolerated, but it can cause some side effects. Common issues include lightheadedness or dizziness, and some individuals might feel tired or confused. In rare cases, more serious problems, such as a slow heart rate or changes in blood pressure, can occur. Propranolol's use in other health conditions supports its safety. However, individuals with asthma should exercise caution, as it might cause breathing problems. Always consult a doctor if any side effects occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores how propranolol affects vascular responses during menopause, a new angle for managing symptoms. While most treatments for menopause focus on hormone replacement to alleviate symptoms, propranolol, a beta-blocker, is being investigated for its potential to directly influence blood vessel function. This approach could offer a non-hormonal alternative, which is significant for individuals who cannot or prefer not to use hormone-based therapies. By examining how propranolol interacts with conditions like hypoxia and hypercapnia, researchers hope to uncover new ways to manage menopause symptoms effectively.

What evidence suggests that this trial's treatments could be effective for vascular responses in menopause?

Research has shown that propranolol, which participants in this trial may receive, can reduce the frequency and severity of hot flashes and similar symptoms in menopausal women. Studies have found that propranolol is usually safe, with only minor side effects. It is also often used to treat high blood pressure and some heart conditions. Its potential to help with menopause symptoms arises from its ability to block certain receptors in the body that respond to stress hormones. This action may help manage the changes in blood flow that occur during menopause. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for women assigned female at birth who are premenopausal, perimenopausal, or postmenopausal. Participants should have a healthy weight with a BMI between 18 and 30 kg/m2. The study aims to understand how aging and menopause affect blood vessel responses during low oxygen conditions.

Inclusion Criteria

My BMI is between 18 and 30.

I was assigned female at birth.

I am before, during, or after menopause.

Exclusion Criteria

Pregnancy, breastfeeding

Body mass index >30 kg/m2

Current smoking/Nicotine/Drug use

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are exposed to hypoxia, hypercapnia, and cold pressor test to examine vascular responses

1-2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gemtesa
• Placebo
• Propranolol

Trial Overview

The study is testing the effects of Propranolol (a beta-blocker), Gemtesa (used for overactive bladder), and a placebo on blood vessel dilation in hypoxic conditions among different stages of menopause. It's designed to see if these drugs influence the body's response to low oxygen.

How Is the Trial Designed?

Group I: Hypoxia Experimental Treatment 3 Interventions

Participants will be exposed to hypoxia (low oxygen air) using a mask.

Group II: Hypercapnia Experimental Treatment 3 Interventions

Participants will be exposed to hypercapnia (high carbon dioxide air) using a mask.

Group III: Cold pressor test Experimental Treatment 3 Interventions

Participants will be exposed to the cold pressor test (ice water on the foot).

Gemtesa is already approved in United States for the following indications:

Approved in United States as Gemtesa for:

• Overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Published Research Related to This Trial

A study involving six healthy adult volunteers tested four different brands of propranolol (Inderal, Ciplar, Corbeta, and Propal) to assess variations in how the body absorbs and responds to the medication.

The results showed no significant differences in the pharmacokinetic (how the drug is processed in the body) and pharmacodynamic (the drug's effects on the body) parameters among the brands, indicating they are likely interchangeable in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. Biswas, NR., Garg, SK., Kumar, N., et al.[2013]

Propranolol, at lower doses of 40 and 80 mg, significantly impaired cognitive performance in tasks like simple reaction time and digital copying tests, indicating central effects on mental function.

Higher doses of propranolol (160 and 320 mg) showed reduced efficacy in impairing cognitive tasks and even worsened performance in some cases, suggesting that lower doses may be more effective for certain central effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central effects of single oral doses of propranolol in man. Salem, SA., McDevitt, DG.[2019]

In a study involving mature female Wistar rats, propranolol showed beneficial effects on the skeletal system regardless of the estrogen status, suggesting its potential as a treatment for bone health.

In vitro experiments indicated that while propranolol positively affects bone properties, it may have antagonistic interactions with estradiol, highlighting the complexity of its effects on bone metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do effects of propranolol on the skeletal system depend on the estrogen status? Sliwiński, L., Folwarczna, J., Pytlik, M., et al.[2020]

In a study of 110 patients with mild to moderate hypertension, Clinoril (sulindac) did not reduce the effectiveness of propranolol in lowering blood pressure, while piroxicam significantly increased diastolic blood pressure compared to both Clinoril and placebo.

Patients treated with piroxicam experienced a sustained increase in diastolic blood pressure, indicating that it may interfere with the antihypertensive effects of propranolol, unlike Clinoril which showed no such effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Clinoril (sulindac, MSD), piroxicam and placebo on the hypotensive effect of propranolol in patients with mild to moderate essential hypertension. Ebel, DL., Rhymer, AR., Stahl, E., et al.[2019]

Propranolol is a versatile noncardioselective β-blocker used to treat various conditions, including hypertension, anxiety disorders, and migraine prophylaxis, highlighting its efficacy in managing both cardiovascular and non-cardiovascular symptoms.

The study provides a comprehensive profile of propranolol, detailing its physicochemical properties and pharmacological actions, which are essential for understanding its therapeutic uses and potential interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol. Al-Majed, AA., Bakheit, AHH., Abdel Aziz, HA., et al.[2017]

Inderectic, a combination of propranolol and bendrofluazide, significantly reduced blood pressure more effectively than either medication alone in a study of 21 hypertensive patients.

The study found that Inderectic was as effective as the same medications taken separately, with only minor side effects reported and no patients needing to withdraw from the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fixed combination of propranolol and bendrofluazide in the treatment of hypertension. Jäättelä, A.[2013]

Propranolol lowers arterial pressure by decreasing sympathetic nervous activity, suggesting that its hypotensive effect involves action within the central nervous system (CNS).

The study indicates that this central action is related to beta-adrenoceptor blockade, as the dextro isomer of propranolol does not produce the same effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central hypotensive effect of propranolol. Dollery, CT., Lewis, PJ.[2013]

In a study involving 51 patients, both long-acting formulations of propranolol significantly reduced the frequency of migraine attacks compared to placebo, demonstrating their efficacy in migraine management.

The higher dose formulation (Inderal LA 160 mg) was more effective than the lower dose (Half-Inderal LA 80 mg) in reducing migraine frequency, with no significant difference in side effects between the two formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses. Carroll, JD., Reidy, M., Savundra, PA., et al.[2017]

In two pharmacokinetic studies involving 48 healthy volunteers, newly formulated generic propranolol HCl tablets were found to have the same rate and extent of absorption as the brand Inderal tablets, indicating bioequivalence.

Both studies showed no statistically significant differences in key pharmacokinetic parameters (AUC, Cmax, tmax, and Cmin) between the test and reference tablets, confirming that the generic formulation is as effective as the branded version.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of propranolol hydrochloride tablet formulations: application of multiple dose crossover studies. Eldon, MA., Kinkel, AW., Daniel, JE., et al.[2019]

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Propranolol for Vascular Responses in Menopause

Propranolol has been studied in various forms and doses, showing that it is generally safe for humans with only minor side effects reported.

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This medicine may increase the risk of heart or blood vessel problems (eg, bradycardia, hypotension). Check with your doctor right away if your ...